Serum rescues surgical manipulation induced intestinal barrier permeability greater than interleukin 1 receptor antagonist conditioned serum in large animal model

Abstract

Surgical manipulation induced intestinal barrier permeability has been previously demonstrated in rodent models and may prove crucial in the development of postoperative complications such as postoperative ileus and sepsis. However, the observation of this phenomena in a large animal model, and further understanding of mechanisms as well as potential therapeutic approaches has yet to be fully explored. The enteric glial cell population may prove to be a critical participant as they sense the intestinal environment and communicate rapidly with surrounding cell populations. Blockade of glial IL-1 receptor has proven successful in preventing postoperative ileus, a possible sequela of barrier permeability, in a rodent model. Therefore, we hypothesized that a large animal model would demonstrate surgical manipulation-induced intestinal barrier permeability, which could be prevented by luminal injection of interleukin 1 receptor antagonist conditioned serum (IRAP). Ischemia was first induced in the distal jejunum of 6–8-week-old pigs to mimic the disease process that would require intestinal surgery. Jejunum proximal and distal to the ischemic loops was then manipulated by “milking” the intestinal contents and applying friction to the serosa with sterile gauze with and without the injection of 1ml of nonconditioned porcine serum or IRAP into the proximal or distal loop. Forty-five minutes after manipulation, the tissues were collected for immunofluorescence histology and mounted on Ussing chambers to measure transepithelial electrical resistance (TEER) which directly corresponds to mucosal barrier resistance. TEER values for the manipulated proximal intestine were significantly more permeable than control tissue (p<0.0001). In addition, preliminary fluorescent quantification has indicated an increase in glial marker, glial fibrillary acidic protein, in the manipulated tissue (p =0.0499). TEER values for manipulated distal tissue trended towards increased permeability compared to control tissue (p=0.1995). Addition of IRAP significantly increased the resistance of the proximal loop compared to manipulation alone (p=0.0003). Interestingly, addition of control porcine serum significantly increased the resistance of both the proximal and distal loops compared to manipulation alone, and to a greater extent than IRAP (p= <0.0001 and 0.0008 respectively).While the effects of IRAP on interleukin 1 signaling may play a role in prevention of surgical manipulation induced intestinal barrier permeability, it appears than non-conditioned serum may offer therapeutic benefits. Ongoing studies will focus on determining the mechanism of this therapeutic effect on the intestinal epithelia and glia population. NIH K01 OD 028207, NIH-NICHD R01 HD095876 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.